This article reviews the evidence that homocysteine is a risk factor for coronary artery disease. This evidence ranges from that obtained from in-vitro experiments sometimes using non-physiological concentrations of homocysteine to epidemiological studies involving large numbers of subjects. Despite the variety of studies and methodologies employed, the hypothesis that homocysteine is a risk factor remains plausible. The relationship between certain nutrients and serum homocysteine and the therapeutic implications of this relationship are discussed.